The actions of the hormone, calcitonin, on bone and calcium metabolism

Project Details

Maintenance of extracellular calcium within strict limits is central to life. Surprisingly, for such a critical aspect of physiology, the regulation of calcium homeostasis throughout life is not fully understood. Bone is the major store of calcium in the body and, as such, contributes significantly to the maintenance of calcium homeostasis. The balance between the two tightly coupled processes of bone formation, mediated by osteoblasts, and bone breakdown (resorption), mediated by osteoclasts, is an important determinant of the amount of calcium either stored or released from bone.

The predominant action of the calciotropic hormone, calcitonin, has been regarded as the inhibition of osteoclastic bone resorption. These effects have been observed with exogenous calcitonin and the physiological roles of calcitonin have not been amenable to study. Significant progress however, has been made by our own and several other groups, by developing mouse models in which the calcitonin gene or its target, the calcitonin receptor (CTR) gene have been genetically modified. Together, data from these studies allow the proposition that calcitonin has important and related physiological roles in (a) protecting the skeleton by regulating bone metabolism and (b) maintaining calcium homeostasis. Specifically, one of the intriguing actions of calcitonin identified in these studies is its action to inhibit bone formation. These insights represent a significant advance in our understanding of the physiological role of calcitonin and the CTR, but many questions remain regarding the mechanism of action of calcitonin.

In this project, we will focus on one of the functions of calcitonin that we believe to be of particular physiological importance, that is the potential actions of calcitonin to regulate bone formation centrally. The aim of this study is to define the physiological role of the CTR expressed in the brain in inhibiting bone formation. This will be achieved by extensively characterising the bone phenotype of a genetically modified mouse model in which the target for calcitonin action, the CTR has been specifically deleted in the hypothalamus in mice. Significance: This study will significantly advance our understanding of the physiological role of calcitonin, which is important in appreciating the totality of calcium homeostasis in the body and, equally important, in unravelling the control of bone formation. Techniques include: Quantitative Real Time PCR (Q-PCR), bone analyses including microCT, biomechanical strength analyses, static and dynamic histomorphometry and biochemical analyses.

Research Opportunities

This research project is available to Honours students to join as part of their thesis.Please contact the Research Group Leader to discuss your options.